BPH-related false positive of <sup>68</sup>Ga-PSMA PET/CT in the diagnosis of prostate cancer: The Achilles heel of biopsy-free radical prostatectomy?
Authors: Wei Tang, Yongxiang Tang, Lin Qi, Ye Zhang, Guyu Tang, Xiaomei Gao, Shuo Hu, Yi Cai
Journal: Journal of Clinical Oncology (2023)

319 Background: Radical prostatectomy (RP) is the primary treatment for localized clinically significant prostate cancer (csPCa). However, its application is generally based on prior pathological diagnosis. 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga-PSMA PET/CT) has recently been found to have high diagnostic efficacy and is considered promising in biopsy-free RP. Notably, inadequate specific or positive predictive value of imaging diagnosis strategy could become the Achilles’ Heel of biopsy-free RP. For 68 Ga-PSMA PET/CT, the expression of PSMA in benign prostatic hyperplasia (BPH) tissue and its related positive reaction, which can reduce the specificity of diagnosis, are important concerns affecting the imaging diagnosis of PCa as well as the feasibility of biopsy-free RP. Currently, no study has explored the BPH-related false positive rate of 68 Ga-PSMA PET/CT in the detection of PCa. Furthermore, the influence of maximum standardized uptake value (SUVmax) on biopsy-free RP is also poorly characterized. Methods: To investigate BPH-related false positive rate of 68 Ga-PSMA PET/CT in detecting PCa and the influence of SUVmax on biopsy-free RP, a retrospective descriptive observational study was conducted. Patients who received 68 Ga-PSMA PET/CT because of clinical suspicion of PCa based on elevated prostate-specific antigen (&gt; 4ng/ml) or abnormal digital rectal examination and subsequently were confirmed to be BPH or PCa by systematic biopsy or targeted biopsy (TB) were included. The receiver operating characteristic curve was generated for SUVmax values, from which the area under the curve (AUC) and the Youden index was calculated. Sensitivity and specificity were calculated based on the cutoffs. Results: A total of 89 BPH and 94 PCa patients who met the inclusion criteria were included. 27 of the 89 BPH cases were considered 68 Ga-PSMA PET/CT positive, all dominant lesions were confirmed to be BPH tissue through TB, and thus, were regarded as BPH-related false positive. The BPH-related false positive rate of 68 Ga-PSMA PET/CT in the detection of PCa was 30.3%. SUVmax could effectively distinguish BPH and grade group (GG) one patients with an AUC of 0.8562 and could potentially benefit biopsy-free RP by avoid BPH-related misdiagnosis and GG one-related overtreatment. The optimal SUVmax cutoff value was 9.750 with a sensitivity of 64.71% and a specificity of 97.22%. Given the pivotal role of specificity in biopsy-free RP, we investigated the optimal SUVmax cutoff under when the specificity was 100%. The result was 14.60, with a sensitivity of 41.18% and a specificity of 100%. Conclusions: Our results revealed, for the first time, the BPH-related false positive rate of 68 Ga-PSMA PET/CT in the primary diagnosis of PCa. Using SUVmax values in biopsy-free RP can effectively exclude both BPH and GG one patients.